Aldosterone, the Mineralocorticoid Receptor, and Cardiovascular Disease in Obesity

NCT04519164 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2020P002311
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate whether the mineralocorticoid receptor antagonist eplerenone, when compared to chlorthalidone plus potassium chloride, can improve cardiac MRI-derived myocardial perfusion reserve and fibrosis, independent of blood pressure, and proportionately to the severity of autonomous aldosterone production.

Conditions

Metabolic Syndrome; Hypertension; Overweight and Obesity

Keywords

aldosterone; mineralocorticoid receptor antagonist

Outcome Measures

Primary Outcomes (1)

• Change in Stress Myocardial Perfusion Reserve on Cardiac MRI

  Change in myocardial perfusion reserve

  one year

Secondary Outcomes (1)

• Change in Extracellular Volume Fraction

  one year

Study Arms (2)

Eplerenone

EXPERIMENTAL

Participants will receive eplerenone, ranging from 25-100mg daily for one year.

Drug: Eplerenone

Chlorthalidone with potassium chloride

ACTIVE COMPARATOR

Participants will receive chlorthalidone (6.25-25mg daily for one year) along with potassium chloride (up to 20 mEq daily for one year)

Drug: Chlorthalidone with potassium chloride

Interventions

Eplerenone DRUG

mineralocorticoid receptor antagonist and potassium-sparing diuretic

Also known as: Inspra

Eplerenone

Chlorthalidone with potassium chloride DRUG

potassium-wasting diuretic with potassium chloride

Also known as: hygroton

Chlorthalidone with potassium chloride

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI ≥ 30 with at least one of the following, or BMI ≥ 25 with at least two of the following:
• Untreated Hypertension: Stage I (BP 120-139/80-89 mmHg) or stage II (BP 140-159/90-99 mmHg).
• Treated Hypertension: On one anti-hypertensive medication with BP\<140/90 mmHg and willing to undergo a 2-week washout of the medication before initiating eplerenone or chlorthalidone + KCl
• Dysglycemia: Impaired fasting plasma glucose (100-125 mg/dL) or glycated A1c 5.7-6.4%
• Dyslipidemia: Fasting triglyceride level \> 150 mg/dL and HDL\< 40 mg/dL in men or \<50 mg/dL in women.
• Age between 18 and 70 years old

You may not qualify if:

• Estimated glomerular filtration rate \< 60 mL/min/1.73m2)
• Serum potassium \> 5.2 mEq/L
• Known diagnosis or treatment for type 1 or type 2 diabetes
• Known history of CVD (myocardial infarction, heart failure, atrial fibrillation, or stroke)
• EKG with ischemic ST-segment or T-wave changes or Q waves in more than one territorial lead or a left bundle branch block
• Pregnancy (verified with a pregnancy test) or breast-feeding

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Metabolic Syndrome; Hypertension; Overweight; Obesity

Interventions

Eplerenone; Chlorthalidone; Potassium Chloride

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Limitations and Caveats

Limitations: * this was a one year study: longer durations of treatment may have shown different results * the population was selected because they were known to be free of cardiac and coronary disease: the absence of these high risk features may have made potential treatment effects to small to detect * cardiac MRI was used as a surrogate of clinical events

Results Point of Contact

• Title: Anand Vaidya
• Organization: Brigham and Women's Hospiptal, Mass General Brigham

anandvaidya@bwh.harvard.edu

6177325666

Study Officials

• Anand Vaidya, MD

  Brigham and Women's Hospital, Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: study medications will be blinded to the participant, investigator, outcomes assessors, and the care providers of the participants. Only the research pharmacists who prepare the study medications will be aware.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Participants will be randomized to receive either eplerenone or chlorthalidone with potassium chloride

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 19, 2020
• Study Start: December 1, 2020
• Primary Completion: September 17, 2025
• Study Completion: September 17, 2025
• Last Updated: September 15, 2026
• Results First Posted: September 15, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)